Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne illness in the United States. B. burgdorferi sensu stricto causes disease in North America; B. garinii and B. afzelii are more common in Europe. Ixodes ticks transmit the disease: I. scapularis, which also transmits babesiosis and anaplasmosis, is found in the northeastern and midwestern United States; I. pacificus is found in the western United States. The white-footed mouse is the preferred host for larval and nymphal ticks. Adult ticks prefer the white-tailed deer as host. The tick must feed for 24 h to transmit the disease.

Clinical Features

EARLY INFECTION, STAGE 1: LOCALIZED INFECTION
After an incubation period of 3-32 days, erythema migrans (EM) develops at the site of the tick bite in 80% of pts. The classic presentation is a red macule that expands slowly to form an annular lesion with a bright red outer border and central clearing; central erythema, induration, necrosis, or vesicular changes or many red rings within an outer ring are also possible.

EARLY INFECTION, STAGE 2: DISSEMINATED INFECTION

• Hematogenous spread occurs within days to weeks after infection. Secondary annular lesions may develop.
• Pts develop headache, mild neck stiffness, fever, chills, migratory musculoskeletal pain, arthralgias, malaise, and fatigue. These symptoms subside within a few weeks, even in untreated pts.
• Meningeal irritation: CSF is initially normal; however, weeks to months later, ~15% of pts progress to frank neurologic abnormalities (meningitis; encephalitis; cranial neuritis, including bilateral facial palsy; motor or sensory radiculoneuropathy; mononeuritis multiplex; ataxia; and myelitis).
• Cardiac involvement occurs in ~8% of pts. Atrioventricular (AV) block of fluctuating degree is most common, but acute myopericarditis is possible.

• Lyme arthritis develops in ~60% of untreated pts in the United States. It usually consists of intermittent attacks of oligoarticular arthritis in large joints (especially the knees) lasting weeks to months. Joint fluid cell counts range from 500 to 110,000/μL. Recurrent attacks decrease yearly, but a few pts have chronic arthritis with bony and cartilage erosion. Arthritis can persist despite eradication of spirochetes.
• Chronic neurologic involvement is less common. Encephalopathy affecting memory, mood, or sleep can be accompanied by axonal polyneuropathy manifested as either distal paresthesia or spinal radicular pain. In Europe, severe encephalomyelitis is seen with B. garinii infection.
• Acrodermatitis chronica atrophicans, a late skin manifestation, is seen in Europe and Asia and is associated with B. afzelii infection.

Diagnosis

• Culture of the organism in Barbour-Stoenner-Kelly medium is largely a research tool. Cultures are positive only early in illness, with the organism isolated primarily from EM skin lesions.
• Polymerase chain reaction (PCR) is most useful for joint fluid, is less sensitive for cerebrospinal fluid (CSF), and has little utility for plasma or urine testing.
• Serology can be problematic because tests do not clearly distinguish between active and inactive infection. Serologic testing should be undertaken when the pt has at least an intermediate pretest likelihood of having Lyme disease.
• Two-step testing: enzyme-linked immunosorbent assay (ELISA) screening with Western blot testing in cases with positive or equivocal results. IgM and IgG testing should be done in the first month of illness, after which IgG testing alone is adequate.

Treatment

Except for neurologic and cardiac disease, most treatment can be oral.

1. Doxycycline (100 mg bid) is the agent of choice for men and nonpregnant women and is also effective against anaplasmosis.
2. Amoxicillin (500 mg tid), cefuroxime (500 mg bid), erythromycin (250 mg qid), and newer macrolides are alternative agents, preferred in that order.
3. More than 90% of pts have good outcomes with a 14-day course of treatment for localized infection or a 21-day course for disseminated infection.
4. Neuroborreliosis: IV treatment with ceftriaxone (2 g/d for 14-28 days) should be given. Cefotaxime or penicillin is an alternative.
5. Pts with high-degree AV block should receive a 28-day course that commences with IV ceftriaxone (or alternative IV drugs) until the high-degree AV block has resolved; oral agents can then be used to complete treatment.
6. Lyme arthritis: 30-60 days of PO antibiotic. For pts who do not respond to oral agents, re-treatment with IV ceftriaxone for 28 days is appropriate. If joint inflammation persists after therapy but PCR testing for B. burgdorferi DNA in joint fluid gives negative results, anti-inflammatory agents or synovectomy may be successful.
7. Chronic Lyme disease: Persistent musculoskeletal and neurocognitive symptoms with fatigue occur in a small percentage of pts after antibiotic treatment. Further antibiotic courses are not helpful; treatment consists of symptom-based supportive care.

Prophylaxis

If an attached, engorged I. scapularis nymph is found or if follow-up will be difficult, a single 200-mg dose of doxycycline, given within 72 h of the tick bite, effectively prevents the disease. This measure is not routinely recommended.

Prognosis

Early treatment results in an excellent prognosis. Although convalescence is longer the later antibiotics are given, the overall prognosis remains excellent, with minimal or no residual deficits. Reinfection can occur. No vaccine is commercially available.